Is CA14 p.Tyr24Phe (c.71A>T) pathogenic?

CA14 p.Tyr24Phe (c.71A>T) is classified Uncertain significance in CA14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: ambiguous (0.4504); Very rare (popmax 0.00212%, nfe).

How common is CA14 p.Tyr24Phe (c.71A>T) in the general population?

CA14 p.Tyr24Phe (c.71A>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about CA14 p.Tyr24Phe (c.71A>T)?

AlphaMissense predicts ambiguous (score 0.4504) — an in-silico prediction, not a clinical call.

CA14 p.Tyr24Phe

c.71A>T · VCV3483747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4504	ambiguous
REVEL	0.454	indeterminate
SaProt	LLR -10.80	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,527 bp · p 0.45 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,890 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00171% 25/1,461,606 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CA14
Protein: p.Tyr24Phe
Coding: c.71A>T
MANE Select: NM_012113
Type: single nucleotide variant
Location: chr1:150260166 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB
Residue 24: a β-strand; the alpha-carbonic anhydrase domain

Full CA14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA14 p.Glu149= Benign ★★ same type
CA14 p.Ala158Gly Uncertain significance ★ ⚠ same type
CA14 p.Ala173Val Uncertain significance ★ ⚠ same type
CA14 p.Arg101Gln Uncertain significance ★ ⚠ same type
CA14 p.Arg211Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg211His Uncertain significance ★ ⚠ same type
CA14 p.Arg232Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg264Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ca14-p-tyr24phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown